How sex chromosomes get trapped into nonrecombination

Suppression of recombination along the Y chromosome leads to its degeneration, so why does a process with such potentially deleterious consequences arise? In this issue of PLOS Biology, a new model reveals how and why this might be.

with more mutation-laden counterparts. The most likely mechanism of recombination suppression is inversion of a part of the chromosome, which prevents DNA to pair properly during meiosis. As most deleterious mutations cause loss of function, they are largely recessive and have much stronger effects when homozygous. Thus, individuals carrying "lucky" inversions are favored as long as the frequency of the inversion in the population is low and homozygotes for it are very rare. However, as the frequency increases, homozygosity results in strong counterselection, which prevents such inversions to become fixed on autosomes.
However, as Jay and colleagues show, in the vicinity of a sex-determining locus, the result is quite different (Fig 1). Such loci are particular, because heterozygous individuals (XY) reproduce with homozygous individuals (XX), and the sex-determining locus on the Y never occurs as homozygote. Thus, a "lucky" inversion that encompasses this locus only experiences the positive effects related to heterozygote advantage and not the counterselection due to homozygosity. It can thus be fixed on the Y chromosome. Of course, it will experience the well-known disadvantages of recombination suppression, which lead inevitably to degeneration. But once the inversion is fixed, it's too late: The only way out would be to restore recombination by the exact reversal of the inversion, which Jay and colleagues show to be very unlikely in most cases.
Surely, the selection of the inversion and the accumulation of deleterious mutations on it occur simultaneously, and the exact outcome (fixation or loss of the inversion) depends on the balance of these, and on chance. But, although the probability of fixation might be small, the result is irreversible. And it can occur repeatedly, leading to so-called evolutionary strata [6]. The model is applicable to other so-called "supergenes," including ZW sex chromosomes and mating type loci.
Two other convincing models have been published recently, in which the suppression of recombination initially evolves without selection for sexual specialization. Jeffries and colleagues [7] consider that the accumulation of sequence divergence, possible when the recombination rates are lower around the sex-determining locus, can by itself reduce the probability of recombination, creating a positive feedback loop leading to the complete loss of recombination. This model is attractive because it doesn't require inversions to happen, but it is not clear if the process can occur in reality. Lenormand and Roze [8] also considered fixation of recombination suppression (e.g., inversions) around a sex-determining locus due to less mutational load, as in the model of Jay and colleagues (Fig 1). However, they identify an entirely different mechanism that prevents the restoration of recombination: This happens through the evolution of dosage compensation, even in the absence of sex-specific optima for gene expression. The processes described in these models can occur together, and none forbid sex-antagonistic selection, which could thus also interfere.
There are important differences between nonrecombining regions; for example, in plant sex chromosomes, large nonrecombining regions can evolve quite quickly in some species, leading to very different X and Y chromosomes, while other, much older sex chromosomes have only small nonrecombining regions [9]. The reasons for these differences are not yet understood. Could these new models shed new light on this enigma? According to Jay and colleagues, selection during a haploid phase in the life cycle (plants), as well as the turnover of degenerated alleles in multiallelic systems (e.g., genetic self-incompatibility), could limit the expansion of the nonrecombining region. Furthermore, population size, the degree of outcrossing, and sexual dimorphism could play a role. Finally, inherently genomic features such as the distribution of recombination events along the genome, or the frequency and size of inversions, certainly influence the dynamics of recombination suppression, but these features have only been quantified in a few model species. A clear-cut answer is unlikely to emerge as the observed variation is large, even within clades, so the characterization of recombination suppression in more species is necessary to understand the interaction of the multiple factors involved.